Abstract P330: Two Rodent Models Of Augmented 24-hour Blood Pressure Variability Showing Similar Pathophysiological Features: Rats Infused With Norepinephrine Or Angiotensin II

Abstract

Background: Augmented fluctuation of blood pressure (BP), so-called BP variability (BPV), was shown to be associated with cardiovascular diseases independently of BP levels. Recently we reported that 24-h BP variability is augmented in rats continuously infused with norepinephrine (NE) or angiotensin II (Ang II), assuming these animals as models of augmented BPV seen in ambulatory BP monitoring (ABPM) of humans. This study was aimed to clarify the underlying mechanisms for augmented BPV and the effects of azelnidipine, a calcium channel blocker, in rats infused with Ang II or NE. Methods and Materials: Nine-week-old male Wistar rats were continuously infused with subcutaneous 30 μg/h NE or 5.2 μg/h Ang II with or without oral administration with 30 mg/kg/day azelnidipine (Azl) for 14 days (n=8 to 9 per group). BPV was evaluated before and after 14 days of the infusions, using standard deviations (SDs) of systolic and diastolic BP (SBP and DBP) recorded every 15 min under an unrestrained condition by a radiotelemetry system. Baroreceptor reflex sensitivity (BRS) was quantified with a sequence analysis, while sections of the aortic arch, where baroreceptors are thought to be located, were microscopically evaluated by computerized measurement. Results: Both SBP and DBP rose following infusion of NE or Ang II, while these increases were attenuated by Azl (P<0.01). SDs of SBP at the light (L) and dark (D) cycles were increased by NE (L, +94%; D, +117%, P<0.01) and Ang II (L, +94%; D +95%, P<0.01), with similar changes in SDs of DBP. These increases in SDs were attenuated following treatment with Azl almost to the control level (P<0.01). Augmented BPVs in both the NE and Ang II groups were accompanied by reductions in BRS (P<0.05) and by thickened medial area of the aortic arch (P<.0.01), while Azl alleviated impairment of BRS and aortic medial thickening (P<0.05). When analyzed for all groups by a simple regression, augmented BPV correlated with impairment of BRS (r=-0.54, P<0.01), which was associated with aortic medial area (r=-0.56, P<0.01). Conclusion: Rats infused chronically with NE or Ang II are models of increased 24-h BPV, both of which similarly showed impaired BRS and thickening medial layer of the aortic arch in association with augmented BPV.